Discovery of an MLLT1/3 YEATS Domain Chemical Probe
YEATS domain (YD) containing proteins are an emerging class of epigenetic targets in drug discovery. Dysregulation of these modified lysine-binding proteins has been linked to the onset and progression of cancers. We herein report the discovery and characterisation of the first small-molecule chemical probe, SGC-iMLLT, for the YD of MLLT1 (ENL/YEATS1) and MLLT3 (AF9/YEATS3). SGC-iMLLT is a potent and selective inhibitor of MLLT1/3–histone interactions. Excellent selectivity over other human YD proteins (YEATS2/4) and bromodomains was observed. Furthermore, our probe displays cellular target engagement of MLLT1 and MLLT3. The first small-molecule X-ray co-crystal structures with the MLLT1 YD are also reported. This first-in-class probe molecule can be used to understand MLLT1/3-associated biology and the therapeutic potential of small-molecule YD inhibitors.
Synthesis and antimicrobial activity of some new piperidinyl benzimidazoles
A series of 2-(4-methylpiperidin-1-yl)-1,5(6)-disubstituted-1H- benzimidazoles (1-18) were prepared through the reaction of 2-chloro (or 2- chloromethyl)-1H-benzimidazole derivatives with 4-methylpiperidine. For the preparation of the individual isomers,
Kus,Goker,Ayhan,Ertan,Altanlar,Akin
p. 413 - 417
(2007/10/03)
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